Last year we reported that collaborative studies were underway examining the functional activation of the cerebral cortex during performance of a mental rotation task was studied in four healthy human subjects using high field magnetic resonance imaging at 4 Tesla and echo planar imaging. These studies have been largely completed at the present time: Twelve healthy right-handed subjects were studied on a 4 Tesla whole body system using actively shielded head gradients and a homogeneous RF coil. First, sagittal anatomic images were acquired to define the location of the AC and PC and to determine the position of slices for functional imaging. For functional imaging studies, imaging planes were chosen to be oblique, parallel to the line defined by the AC-PC line. T2*-weighted images were acquired during three consecutive periods; resting "Control", "Task", and recovery "Control". For the Task period, the experimental conditions of the original Shepard and Meltzer paradigm were reproduced (1): Pairs of 3-D objects were projected and the subject had to decide whether the objects were identical or mirror images and press one of two buttons on a specially designed keypad. The response and the reaction time for each trial were recorded. During each 'Control' period, a pair (always the same) of identical 2-D objects was repeatedly projected. Although no decision was required, the subject was again instructed to press a button on the keypad. The purpose of this design for the control period was (a) to produce a visual display similar to that used in the task, but which would not require any mental rotation and (b) to produce the same kind of motor response as in the task period. Functional activation maps were generated by using Student's t-test. Functional maps were then superimposed to anatomic images. The various areas of the brain in each subject were identified from the anatomic images, based on the standardized Talairach atlas. All 12 subjects performed mental rotation at two different sessions; one is inside the magnet during the functional imaging session, and the other is outside of the magnet at a separate time. No significant difference in the performance inside the magnet, compared to the performance outside the magnet, was observed. The percentage of errors was 12.0 +/- 8.6 SD % (ranged between 2 and 32%). The reaction time increased linearly with the angular difference, which was 12.0 +/- 4.0 msec/degree (ranged 5.5-17.9 msec/degree). In functional imaging studies, a signal increase in the parietal cortex (mainly Brodmann's area 7) was observed in all 12 subjects. In seven subjects, the activation seemed to be greater in the left parietal lobe. In three subjects it seemed to be more on the right side. Another relatively common finding was bilateral activation in Brodmann's area 19 of the occipital lobe . Activation in area 7 of the parietal cortex was the most consistent finding in this study. This is consistent with the general involvement of the parietal lobe in processing visuo-spatial information. More unexpected and controversial is the issue of the relative involvement of right vs the left hemisphere. Various studies in healthy subjects have provided evidence for right hemisphere superiority in mental rotation (3-4). However, other studies either failed to demonstrate any difference or supported a left hemisphere superiority (5). Several hypotheses have been proposed for the discrepancies described above. The role of the complexity of the stimulus has been considered, since the engagement of the left hemisphere seems to increase with more complex stimuli. The direction of rotation is also involved, with left hemisphere superiority for counterclockwise rotation. Another possible explanation might be a hidden verbal or categorical nature of the task. Objects used by Shepard and Meltzer are designed in such a way that they do not resemble digits or numbers. However one cannot eliminate the possibility that the responses of the subject may present a correspondence with verbal answers ('yes' or 'no'). Therefore this issue remains inconclusive. The activation observed in area 19 of the occipital lobe is another interesting finding. This activation was not contiguous to the activation of the parietal lobe and it was not accompanied by activation of the primary visual cortex. Although this activation may also be related to mental rotation, it is more likely that it reflects the processing of the visual information from the three dimensional objects. Shepard & J. Metzler, Science, 171, 701, 1971. Hu & S.-G. Kim, MRM, 30, 512, 1993. Deutsch, et al., Neuropsychologia, 26, 445, 1988. Corballis & R. McLaren, J Expt Psychol, 10, 318, 1984. Fischer & J.W. Pellegrino, Brain Cognition, 7, 1, 1988.